The precise mechanisms of triggering of human B lymphocytes as well as the immunoregulatory events associated with non-specific and antigen specific stimulation have been delineated in normal individuals and abnormalities of cell triggering and immunoregulation have been described in several immunologically mediated diseases. Hybridoma monoclonal antibodies against human mononuclear cell subsets have been produced and these have been successfully employed to precisely delineate immunoregulatory lymphocyte subsets in normals and disease states; they have also been employed to characterize the ontogeny of functional T cell subsets as well as the differentiation levels of malignant transformation of certain lymphoproliferative diseases. The first antigen specific human T cell clones have been established; they are true clones, totally antigen specific and strictly genetically restricted regarding the requirement for antigen presenting cells. Modulation of the functions of lymphocyte subsets by several relevant pharmacologic agents have been defined. Clinical pathophysiologic and therapeutic studies have been performed in the systemic necrotizing vasculitudes and extraordinarily favorable results with the use of cytotoxic agents have been reported.